1. Field of the Invention
The present invention relates to a polypeptide specifically bound to phosphatidylserine and the use thereof, and more particularly, to a polypeptide having an amino acid sequence designated as sequence number 1 and specifically bound to phosphatidylserine, a phosphatidylserine detecting composition containing the polypeptide as an active ingredient, a method of detecting phosphatidylserine using the polypeptide, an apoptotic cell detecting composition containing the polypeptide as an active ingredient, a drug delivery composition containing the polypeptide as an active ingredient, a composition for treatment and prevention of a tumorous disease, and a composition for visualization of a tumorous region.
2. Description of the Related Art
Phosphatidylserine is an important marker by which macrophages recognize and eliminate an apoptotic cell (Schlegel, R. A. et al., Cell Death and Differentiation, 2001, 8:551-563; Lauber, K. et al., Mol Cell 2004, 14: 277-287 Henson, P. M. et al., Curr Biol 2001, 11: R795-805 Grimsley, C. et al., Trends Cell Biol. 2003, 13: 648-656). Normally, the phosphatidylserine exists inside a cell membrane, and when cells receive a death signal or an erythrocyte ages, the phosphatidylserine is exposed to the outside of the cell membrane (Fadeel, B. et al., Cell Mol Life Sci, 2003, 60:2575-2585). Macrophages recognize phosphatidylserine by a receptor on the cell surface and activate phagocytosis (Fadok, V. A. et al., J immunol 1992, 148:2207-2216; Fadok, V. A. et al., Nature 2000, 405:85-90; Park, S. Y. et. al., Cell Death and Differentiation, 2008; 15:192-201).
The phosphatidylserine is exposed to the outside of the cell membrane under the several disease situations besides an apoptotic cell (Zwaal, R. F. A. et al., Cell. Mol. Life Sci 2005, 62:971-988), and there are several examples such as Scott syndrome, antiphospholipid syndrome, sickle cell anemia, thalassemia, stomatocytosis, uremia, kidney stone disease, diabetes, hyperglycemia, virus and microbiological infection, malaria, pre-eclamphosphatidylserineia, hyperbilirubinemia, and neoplasia. Especially, a number of tumor cells show increased expression of phosphatidylserine to the outside of cell membranes (Utsugi, T. et al., Cancer Res. 1991, 15:3062-3066; Rao, L. et al., Thromb Res. 1992, 67:517-531; Sigimura, M. et al., Fibrinolysis. 1994, 5:365-373; Ran, S. et al., Cancer Res. 2002, 62:6132-6140; Woehlecke, H. et al., Biochem J. 2003, 376:489-495), and such expression is more remarkably shown in an undifferentiated tumorigenic cell. Tumor tissue also releases small vessel which exposes phosphatidylserine to the outside of cell membranes (Ran, S. et al., Cancer Res. 2002, 62:6132-6140; Zwaal, R. F. A. et al., Blood. 1997, 89:1121-1132).
Moreover, phosphatidylserine is also observed in a non-apoptotic cell during several physiological processes which occur inside a cell, and there are examples such as activation of a platelet, a myocyte fusion, formation of a syncytial syncytiotrophoblast, immunoglobulin-dependent stimulation of mast cells, and migration of T cells (Fadeel, B. et al., Cell Death Differ 2006, 13:360-2 Ran, S. et al., Int J Radiat Oncol Biol Phys 2002, 54:1479-84 Schlegel, R. A. et al., Cell Death Differ 2001, 8:551-63.). Among them, blocking of phosphatidylserine expressed during activation of a platelet inhibits thrombosis which may be formed by arteriosclerosis. Thus, the blocking of phosphatidylserine may show treatment effect (Cederholm, A. and Frostegård, J., Ann N Y Acad Sci. 2007, 1108:96-103 Cederholm, A. and Frostegård, J., Drug News Perspect. 2007 20(5):321-6). Because of roles of phosphatidylserine, the phosphatidylserine is proposed as a target material for diagnosis, treatment, and treatment trace for a number of situations such as tumoral or inflammatory disease.
Moreover, it is reported that inhibition of recognizing phosphatidylserine increases immunogenicity of cells in irradiated lymphoma cells (Bondanza, A. et al., J Exp Med 2004, 200:1157-65). Therefore, a protein which can be effectively bound to phosphatidylserine inhibits recognition and removal of immunosuppression of phosphatidylserine of an apoptotic cell so as to be used for enhancing effect of apoptotic cell-based vaccines.
We, inventors of this patent application, carried out study and research to find new proteins or fragment on thereof to mark phosphatidylserine. As a result, since we verified that a polypeptide having an amino acid sequence designated sequence number 1 is specifically bound to phosphatidylserine, the present invention is completed.